Patty L. Bonney, BS, RVT, and Kevin Hahn, DVM. Forty-one dogs .... NA. Died. I day post treatment of sq. cell CA rn -I ? Primary tumor surg. removed; met. lesion ...
Cisplatin Therapy in 41 Dogs With Malignant Tumors Deborah W. Knapp, DVM, Ralph C. Richardson, DVM, Patty L. Bonney, BS, RVT, and Kevin Hahn, DVM
Forty-one dogs with a variety of histopathologically diagnosed, measurable tumors were treated with cisplatin (cis-diamminedichloroplatinum, Platinol, Bristol Laboratories, Syracuse, NY 13221-4755) as a single agent a t a dosage of 60 mg/mZ given intravenously a t 3-week intervals. In an attempt to avoid renal toxicity of cisplatin, saline diuresis was induced and maintained for 4 hours before and 2 hours following cisplatin administration. The dogs received one to ten doses of cisplatin. To determine response to therapy and to monitor toxicity of the drug, the dogs were evaluated with physical examinations including tumor measurements, radiography, complete blood counts, platelet counts, urinalyses, serum urea nitrogen concentrations, and serum creatinine concentrations. An overall response rate of 19% was observed. Complete remission occurred in one of 11 dogs with squamous cell carcinomas and one of one dog with a mediastinal undifferentiated carcinoma. Partial remissions were documented in one of I 1 dogs with squamous cell carcinomas, two of three dogs with metastatic osteosarcomas, one of three dogs with nasal adenocarcinomas, and one of one dog with a thyroid adenocarcinoma. Toxic side effects were primarily gastrointestinal in nature, with vomiting occurring 1-6 hours after cisplatin administration in 27 of 41 dogs. Severe anorexia occurred in three dogs, and hemorrhagic diarrhea was observed in one dog. One dog developed grand ma1 seizures and died 3 hours following therapy. Granulocytopenia was documented in six dogs, and thrombocytopenia was observed in four dogs. One dog showed an increase in serum urea nitrogen and creatinine concentrations, but this patient had known pre-existhg renal disease. These observations of response to therapy and toxicity warrant additional clinical trials to further define cisplatin's role in the treatment of canine neoplasia. (Journal of Veterinary Internal Medicine 1988; 2:41-46)
cisplatin's efficacy against squamous cell carcinoma^,^.^ transitional cell carcinomas,8 an ovarian carcinoma,8 and a pleural adenocarcinoma8 in dogs. Toxicities previously documented in dogs have been limited to gastrointestinal toxicity, bone marrow suppression, and renal to ~ ic ity .~ -Forty-one " dogs with a variety of histopathologically diagnosed, measurable tumors were treated with cisplatin by the Purdue Comparative Oncology Program's Clinical Oncology Section. The dogs were evaluated for response to therapy and toxicity of the drug.
CISPLATIN (cis-diamminedichloroplatinum) is a widely used chemotherapeutic agent in man and is most commonly used against testicular, ovarian, transitional cell, and head and neck carcinomas.'-6 Toxicity of the drug in man frequently includes gastrointestinal toxicity, nephrotoxicity, and bone marrow suppression. Less common toxicities include hypomagnesemia, hypocalcemia, cardiac toxicities, hyperuricemia, peripheial neuropathies, seizures, and anaphylactic reactions.'-6 Cisplatin's application to veterinary medicine has recently been described, and the drug is becoming more popular in the treatment of a variety of solid tumors in dogs.'-'' Previous reports have demonstrated
Materials and Methods Forty-one client-owned dogs with 42 histopathologically diagnosed, measurable tumors were treated with cisplatin as a single agent. Although other modalities of treatment were considered, the final choice of therapy was made by the owner based on expense, access to outpatient therapy, and in a few cases, response in dogs with a similar tumor. The drug was given at a dosage of 60
From the Purdue Comparative Oncology Program, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907-7403. Supported in part by Bristol Laboratories, Syracuse, NY 132214755. Reprint requests: Deborah W. Knapp, DVM, Purdue Cnmparative Oncology Program, School of Veterinary Medicine, Lynn Hall, Purdue University, West Lafayette, IN 47907-7403.
41
Squamous cell CA (axillary) Squamous cell CA (tongue) Squamous cell CA (hard palate) Squamous cell CA (tongue) Squamous cell CA (nasal) Squamous cell CA (vagina) Squamous cell CA (nasal) Squamous cell CA (nasal) Squamous cell CA (oral) Squamous cell CA (tonsil) Osteosarcoma
Osteosarcoma
Osteosarcoma
Thyroid AC
Thyroid CA Hepatic CA Nasal AC
3
13
14
15
16
17
18
12
11
10
9
8
7
6
5
4
2
Undifferentiated CA (mediastinum) Squamous cell CA (digit)
Tumor Type
1
Dog No.
8
NA NA 63
PD PD PR
2
T2,NoM I TzNoM I T3NoMo
21
PR
1
63
NA
PR
SD
T 2J oM I
6
4
63
NA
PD PR
NA
NA
PD
I 2
NA
NA
PD
1
NA NA 330
19
s10+
73
40
150
210
3
NA
127
35
21
36
I20
120
72
1
I35
18
126
720
300+
Survival Time (days)
7
NA
NA
NA
NA
NA
NA
NA
NA
42
570
2 10+
Duration Max. Resp. (days)
PD
1
NA
NA
PD
2 PD
NA
NA
1
5
NA
PD
2
42 NA
PR
5
I50
PD
CR
10
84
Time to Max. Resp. (days)
1
CR
Max. Resp.
5
2
~
No. Doses
TxM I
TxM I
TNM Class.
TABLEI . Results of 41 Dogs Treated with Cisplatin
None
Vomiting, granulocytopenia (granulocytes = 1,674/ mm3), thrombocytopenia (platelts = 32,000/mm3) Vomiting, granulocytopenia (granulocytes = 1,908/ mm') Azotemia (BUN = 60 mg/ dl, creat = 2 mg/dl) None
Vomiting
Vomiting
Vomiting
Vomiting
Vomiting
Vomiting
None
Vomiting
Vomiting
Anorexia
Vomiting
Thrombocytopenia(plate1ets37,000/mm3) Vomiting
Toxicity
PD occurred at 393 days; still alive on different therapy
Azotemic before cisplatin therapy; died of cardiac failure Two primary tumors
Primary tumor surg. removed; PD occured at SO days
Primary tumor surg. removed; met. lesion removed 7 days after PR documented died of pneumonia; no evidence of osteosarcoma Primary tumor surg. removed; met. lesions removed 3 days after PR documented
Died I day post treatment of sq. cell CA
Died of malignant lymphoma; no evidence of sq. cell CA; first 6 cisplatin doses were
